Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18,168 people with type 1 diabetes: observational study

Isabelle Steineck, Jan Cederholm, Björn Eliasson, Araz Rawshani, Katarina Eeg-Olofsson, Ann-Marie Svensson, Björn Zethelius, Tarik Avdic, Mona Landin-Olsson, Johan Jendle, Soffia Gudbjörnsdóttir, Swedish National Diabetes Register, Isabelle Steineck, Jan Cederholm, Björn Eliasson, Araz Rawshani, Katarina Eeg-Olofsson, Ann-Marie Svensson, Björn Zethelius, Tarik Avdic, Mona Landin-Olsson, Johan Jendle, Soffia Gudbjörnsdóttir, Swedish National Diabetes Register

Abstract

Objective: To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes.

Design: Observational study.

Setting: Swedish National Diabetes Register, Sweden 2005-12.

Participants: 18,168 people with type 1 diabetes, 2441 using insulin pump therapy and 15,727 using multiple daily insulin injections.

Main outcome measures: Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases.

Results: Follow-up was for a mean of 6.8 years until December 2012, with 114,135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in >80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have influenced the observed association.

Conclusion: Among people with type 1 diabetes use of insulin pump therapy is associated with lower cardiovascular mortality than treatment with multiple daily insulin injections.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: KE-O has received fees from Sanofi and Novo Nordisk for lectures outside the submitted work; ML-O lectures about diabetology and has been paid by different pharmaceutical companies.

© Steineck et al 2015.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4794062/bin/stei024170.f1_default.jpg
Fig 1 Kaplan-Meier crude survival curves in 18 168 individuals with type 1 diabetes according to treatment with insulin pump therapy or multiple daily injections. No of cases and individuals at risk are given in each group
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4794062/bin/stei024170.f2_default.jpg
Fig 2 Kaplan-Meier survival curves for first incident hypoglycaemic events in patients with type 1 diabetes during seven years of follow-up. No of cases and individuals at risk are given for each group

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